| Autor: |
Cuevas-López B; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Romero-Ramirez EI; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., García-Arroyo FE; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Tapia E; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., León-Contreras JC; Experimental Pathology Section, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City 14000, Mexico., Silva-Palacios A; Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Roldán FJ; Outpatient Department, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Campos ONM; Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico., Hernandez-Esquivel L; Department of Biochemistry, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Marín-Hernández A; Department of Biochemistry, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Gonzaga-Sánchez JG; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Hernández-Pando R; Experimental Pathology Section, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City 14000, Mexico., Pedraza-Chaverri J; Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico., Sánchez-Lozada LG; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico., Aparicio-Trejo OE; Department of Cardio-Renal Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico. |
| Abstrakt: |
The incidence of kidney disease is increasing worldwide. Acute kidney injury (AKI) can strongly favor cardio-renal syndrome (CRS) type 3 development. However, the mechanism involved in CRS development is not entirely understood. In this sense, mitochondrial impairment in both organs has become a central axis in CRS physiopathology. This study aimed to elucidate the molecular mechanisms associated with cardiac mitochondrial impairment and its role in CRS development in the folic acid-induced AKI (FA-AKI) model. Our results showed that 48 h after FA-AKI, the administration of N-acetyl-cysteine (NAC), a mitochondrial glutathione regulator, prevented the early increase in inflammatory and cell death markers and oxidative stress in the heart. This was associated with the ability of NAC to protect heart mitochondrial bioenergetics, principally oxidative phosphorylation (OXPHOS) and membrane potential, through complex I activity and the preservation of glutathione balance, thus preventing mitochondrial dynamics shifting to fission and the decreases in mitochondrial biogenesis and mass. Our data show, for the first time, that mitochondrial bioenergetics impairment plays a critical role in the mechanism that leads to heart damage. Furthermore, NAC heart mitochondrial preservation during an AKI event can be a valuable strategy to prevent CRS type 3 development. |
